Journal article
Assessing siRNA Pharmacodynamics in a Luciferase-expressing Mouse
Molecular therapy, Vol.16(12), pp.1995-2001
12/2008
DOI: 10.1038/mt.2008.187
PMCID: PMC3014086
PMID: 18781145
Abstract
A significant barrier to the successful general development of small-interfering RNA (siRNA) therapeutics is the ability to deliver them systemically to target organs and cell types. In this study, we have developed a mouse strain that will facilitate the evaluation of the efficacy of siRNA delivery strategies. This strain contains robust ubiquitous expression of firefly luciferase from germ line Cre-mediated recombination of the ROSA26-LSL-Luc allele. We show that luciferase is highly and uniformly expressed in all tissues examined. Using this mouse model, we describe a facile assay that enables the assessment of the pharmacodynamics of a systemically delivered siRNA formulation. These mice can also be used as universal donors, enabling the efficient and sensitive monitoring of cell trafficking or tissue transplantation. The primary advantage of this approach is that siRNA efficacy against a nonessential target can be easily evaluated in any tissue. This strain should generally enhance the ability to rapidly screen, compare and optimize various siRNA formulations for tissue-targeted or -enhanced systemic delivery in a preclinical development setting.
Details
- Title: Subtitle
- Assessing siRNA Pharmacodynamics in a Luciferase-expressing Mouse
- Creators
- Robert U Svensson - Department of Molecular Physiology and Biophysics and Pathology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, USAZuhair K Ballas - The Iowa City VA Medical Center, Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USAMichael R Shey - The Iowa City VA Medical Center, Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USAMichael D Henry - Department of Molecular Physiology and Biophysics and Pathology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, USAJ Robert Dorkin - Alnylam Pharmaceuticals, Cambridge, Massachusetts, USAMichael Goldberg - David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USAAkin Akinc - Alnylam Pharmaceuticals, Cambridge, Massachusetts, USARobert Langer - David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USADaniel G Anderson - David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USADavid Bumcrot - Alnylam Pharmaceuticals, Cambridge, Massachusetts, USA
- Resource Type
- Journal article
- Publication Details
- Molecular therapy, Vol.16(12), pp.1995-2001
- Publisher
- Elsevier Inc
- DOI
- 10.1038/mt.2008.187
- PMID
- 18781145
- PMCID
- PMC3014086
- ISSN
- 1525-0016
- eISSN
- 1525-0024
- Language
- English
- Date published
- 12/2008
- Academic Unit
- Molecular Physiology and Biophysics; Pathology; Radiation Oncology; Immunology; Urology; Internal Medicine
- Record Identifier
- 9984094510302771
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